Kawasaki Disease: An Update of diagnosis and treatment What is Kawasaki Disease? • Idiopathic multisystem disease characterized by vasculitis of small & medium blood vessels, including coronary arteries Diagnostic Criteria • • Fever for at least 5 days At least 4 of the following 5 features: 1. Changes in the extremities Edema, erythema, desquamation 2. Polymorphous exanthem, usually truncal 3. Conjunctival injection 4. Erythema&/or fissuring of lips and oral cavity 5. Cervical lymphadenopathy • Illness not explained by other known disease process Modified from Centers for Disease Control. Kawasaki Disease. MMWR 29:61-63, 1980 Atypical or Incomplete Kawasaki Disease • • • • • Present with < 4 of 5 diagnostic criteria Compatible laboratory findings Still develop coronary artery aneurysms No other explanation for the illness More common in children < 1 year of age • 2004 AHA guidelines offer new evaluation and treatment algorithm Phases of Disease • Acute (1-2 weeks from onset) – Febrile, irritable, toxic appearing – Oral changes, rash, edema/erythema of feet • Subacute (2-8 weeks from onset) – Desquamation, may have persistent arthritis or arthralgias – Gradual improvement even without treatment • Convalescent (Months to years later) • AHA classify coronary arteries aneurysms – Small (5 mm internal diameter), – medium (5 to 8 mm internal – diameter), – or giant (8 mm internal diameter). • The Japanese Ministry of Health Classify coronary arteries as abnormal • the internal lumen diameter is 3 mm in children 5 years old or 4 mm in children 5 years old; • the internal diameter of a segment measures 1.5 times that of an adjacent segment; Abnormal coronary artery Diameter of CA /BSA Coronary Artery Involvement in Children With Kawasaki Disease: Risk Factors Harada et al – risk score (1) white blood cell count 12 000/mm3; (2) platelet count 350 000/mm3; (3) CRP 3; (4) hematocrit 35% (5) albumin 3.5 g/dL; (6) age 12 months; (7) male sex. 4/7 : high risk ASAI Symtomps 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 0 điểm Sex Nữ Age 1 Days of fever < 14 Recurrent fever Recurrent rash Recurrent bong da Anemie (Hb < 10g/dL) WBC(X 103/ mm3) < 26 VS(mm) < 60 VS and PLT high for a long <1 time(months ) Enlarge CI Abnormal rymth Ischemic myocady pericarditis 9/23 điểm : high risk 1 điểm Nam >1 14 -15 + 26 – 30 60 – 100 2 điểm 16 + + + > 30 > 100 >1 + + + + + ĐIỀU TRỊ ASPIRIN • AHA-2004: 80-100 mg/kg. • Pediatrics-1995: meta-analysis. Control ASA ASA+IVIG 1g/kg ASA+IVIG >1g/kg Ratio Dilated CA after 30 days (n=2547) After 60 days (n=4151) 22.8% ( 95% CI: 20.625%) 17.3%(95% CI: 14.320.2%) 10.3%( 95% CI: 8.312.3%) 2.3%(95% CI: 0.5-4.2%) 17.1%(95% CI: 13.6-20.7%) ASA+ IVIG >1g/kg lieàu duy nhaát IVIG >1g/kg + ASA <80 13%(95% CI: 9-17%) mg/kg IVIG >1g/kg +ASA 9.1% (95% CI: 6.9-11.4%) >80mg/kg 11.1%(95% CI: 8.7-13.6%) 4.4% (95% CI: 2.8-6%) 2.4%(95% CI: 0.5-4.2%) 4.8%(95% CI: 2.3-7.4%) 4%(95% CI: 2.-6.1%) Dilated CA in 30 days Dilated CA in 60 days IVIG (2G/KG/D) < IVIG 1G/KG < ASA IVIG (2G/KG/D) < IVIG 1G/KG < ASA IVIG HIGH DOSE + ASA HIGH DOSE = IVIG HIGH DOSE + ASA LOW DOSE IVIG HIGH DOSE + ASA HIGH DOSE = IVIG HIGH DOSE + ASA LOW DOSE ASPIRIN vs IVIG TỈ LỆ TỔN THƯƠNG MẠCH VÀNH IVIG+ASPIRIN -IVIG HIGH DOSE -IVIG LOW DOSE ASPIRIN CORTICOID 1. Initial CORTICOID vs ASPIRIN. 2. Initial CORTICOID+ ASPIRIN+ IVIG vs ASPIRIN+IVIG. 3. Resistance IVIG. IVIG+ASPIRIN vs IVIG+ASPIRIN+ METHYPREDNISOLON Randomized Trial of Pulsed Corticosteroid Therapy for Primary Treatment of Kawasaki Disease. N Engl J Med 2007;356:663-75. - 30 mg/kg over 2 to 3 hours - IVIG 2g/kg. - Aspirin 80-100mg/kg. Effect and result • Response with IVIG : 90 % • No response with IVIG : 10 % Prediction of Intravenous Immunoglobulin Unresponsiveness in Patients With Kawasaki disease. Circulation 2006;113;2606-2612; published online May 30, 2006; http://circ.ahajournals.org/cgi/content/full/113/22/2606. Kobayashi-2006 Prediction of Intravenous Immunoglobulin Unresponsiveness in Patients With Kawasaki disease. Circulation 2006;113;2606-2612; published online May 30, 2006; http://circ.ahajournals.org/cgi/content/full/113/22/2606. TIÊN ĐÓAN TỔN THƯƠNG MẠCH VÀNH ANTI IVIG • IVIG ONLY 2 g/kg (evidence level C). • STEROID ONLY. • PULSE STEROID + IVIG: Hashino et al + RCT. – 17 patients who did not respond to an initial infusion of 2 g/kg IVIG plus aspirin followed by an additional IVIG infusion of 1 g/kg. – Randomized to receive either a single additional dose of IVIG (1 g/kg) or pulse steroid therapy. – RESULT: • Patients in the steroidgroup had a shorter duration of fever and lower medical costs. • No significant difference in the incidence of coronary arteryaneurysms was noted between the 2 groups, but power to detect a difference was limited. KHÁNG IVIG AHA-2004 recommends 1.Steroid treatment berestricted to children in whom 2 infusions of IVIG have been ineffective in alleviating fever and acute inflammation (evidence level C). 2.The most commonly used steroid regimen is intravenous pulse methylprednisolone, 30 mg/kg for 2 to 3 hours, administered once daily for 1 to 3 days. Acute Kawasaki Disease: Conclusion for Treatment ( AHA 2004) • IVIG: 2g/kg as one-time dose – Beneficial effect 1st reported by Japanese – Mechanism of action is unclear – Significant reduction in CAA in pts treated with IVIG plus aspirin vs. aspirin alone (15-25%3-5%) Acute Kawasaki Disease: Treatment • IVIG – 70-90% defervesce & show symptom resolution within 2-3 days of treatment – Retreat those with failure of response to 1st dose or recurrent symptoms Up to 2/3 respond to a second course Acute Kawasaki Disease: Treatment • Aspirin – High dose (80-100 mg/kg/day) until afebrile x 48 hrs &/or decrease in acute phase reactants – Need high doses in acute phase due to malabsorption of ASA – Dosage of ASA in acute phase does not seem to affect subsequent incidence of CAA Acute Kawasaki Disease: Treatment • Aspirin – Decrease to low dose (3-5 mg/kg/day) for 6-8 weeks or until platelet levels normalize ( evidence level C). – No evidence /effect on CAA when used alone – Due to potential risk of Reye syndrome instruct parents about symptoms of influenza or varicella In case of persistent or recrudescent fever: Repeat dose of IVIG 2 g/kg as single infusion; consider IV methylprednisolone 30 mg/kg once a day; may be repeated as necessary up to a total of three doses